A Convenient and Efficient One-Pot Synthesis of Arylacetones from (E)-3-Aryl-2-methylacrylic Acids by Curtius Rearrangement

Abstract

A convenient and efficient method was developed for the synthesis of arylacetones from (E)-3-aryl-2-methylacrylic acids through a Curtius rearrangement. The Curtius rearrangement of (E)-3-aryl-2-methylacryloyl azides and subsequent hydrolysis proceeded at mild temperatures in a two-phase medium of carbon tetrachloride and water containing a catalytic amount of tetrabutylammonium bromide to give the corresponding derivatives in 82–93% yield.

Key words

arylacetones - Curtius rearrangement - methylarylacrylic acids - phase-transfer catalysis - acryloyl azides

• References and Notes

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• 13 1-Arylacetones 2a–i; General Procedure A well-stirred mixture of the appropriate (E)-3-aryl-2-methyl­acrylic acid 1 (30 mmol) and SOCl₂, (30.3 mmol) in CCl₄ (50 mL) was heated at 35 °C for 30 min. 20% aq NaN₃ (30.3 mmol) and TBAB (0.97 g, 10 mol%) were added at r.t., and the mixture was stirred for another 30 min, then heated to the reflux temperature. When the reaction was complete (1.5–2 h; Table 2), the aqueous layer was separated and extracted with CCl₄ (3 × 20 mL). The organic layers were combined, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, EtOAc–PE). All products were identified by ¹H and ¹³C NMR and MS spectral analysis.
• 14 Meng F, He X, Cao C, Liang J, Zhang T. CN 201610328295.4, 2016
• 15 1-Phenylacetone (2a) Colorless oil; yield: 3.75 g (93%). ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.29–7.34 (m, 2 H), 7.22–7.26 (m, 1 H), 7.18–7.21 (m, 2 H), 3.75 (s, 2 H), 2.12 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 206.2, 135.3, 130.0, 128.7, 126.9, 50.0, 29.7. GC-MS (EI): m/z = 134.2 [M⁺]. 1-(3,4,5-Trimethoxyphenyl)acetone(2b) Faintly yellow solid; yield: 5.78 g (86%), mp 88–91 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 6.49 (s, 2 H), 3.74 (s, 6 H), 3.66 (s, 2 H), 3.63 (s, 3 H), 2.11 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 206.4, 153.1, 136.6, 130.9, 107.2, 60.3, 56.1, 50.3, 29.7. GC-MS (EI): m/z = 224.2 [M⁺]. 1-(3,4-Dimethoxyphenyl)acetone (2c) Yellow oil; yield: 4.78 g (82%). ¹H NMR (600 MHz, DMSO-d ₆): δ = 6.87 (d, J = 8.1 Hz, 1 H), 6.78 (d, J = 1.9 Hz, 1 H), 6.70 (dd, J = 8.1, 2.1 Hz, 1 H), 3.72 (s, 6 H), 3.64 (s, 2 H), 2.09 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 206.7, 149.0, 148.0, 127.7, 121.9, 113.7, 112.2, 55.8, 55.8, 49.7, 29.5. GC-MS (EI): m/z = 194.2 [M⁺]. 1-(4-Methoxyphenyl)acetone (2d) Yellow oil; yield: 4.29 g (87%). ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.08–7.11 (m, 2 H), 6.84–6.89 (m, 2 H), 3.72 (s, 3 H), 3.66 (s, 2 H), 2.08 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 206.7, 158.4, 130.9, 127.2, 114.1, 55.3, 49.2, 29.6. GC-MS (EI): m/z = 164.2 [M⁺]. 1-(2-Methoxyphenyl)acetone (2e) Yellow oil; yield: 4.39 g (89%). ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.19–7.26 (m, 1 H), 7.12 (d, J = 7.3 Hz, 1 H), 6.96 (d, J = 8.3 Hz, 1 H), 6.88 (t, J = 7.3 Hz, 1 H), 3.73 (s, 3 H), 3.64 (s, 2 H), 2.07 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 206.2, 157.5, 131.5, 128.6, 124.2, 120.6, 111.0, 55.7, 45.0, 29.7. GC-MS (EI): m/z = 164.2 [M⁺]. 1-(3-Nitrophenyl)acetone (2f) Yellow solid; yield: 4.57 g (85%); mp 64–66 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 8.04–8.11 (m, 2 H), 7.54–7.65 (m, 2 H), 4.00 (s, 2 H), 2.19 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 205.5, 148.0, 137.6, 137.1, 129.8, 124.8, 121.8, 48.7, 30.1. GC-MS (EI): m/z = 179.2 [M⁺]. 1-(4-Nitrophenyl)acetone (2g) Faintly yellow solid; yield: 4.73 g (88%); mp 203–206 °C. ¹H NMR (600 MHz, DMSO-d ₆): δ = 8.12–8.21 (m, 2 H), 7.37–7.51 (m, 2 H), 3.99 (s, 2 H), 2.19 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 205.2, 146.7, 143.5, 131.5, 123.5, 49.2, 30.2. GC-MS (EI): m/z = 179.2 [M⁺]. 1-(3-Chlorophenyl)acetone (2h) Yellow oil; yield: 4.30 g (85%). ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.32 (t, J = 7.7 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 1 H), 7.26 (s, 1 H), 7.13 (d, J = 7.3 Hz, 1 H), 3.80 (s, 2 H), 2.14 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 205.7, 137.8, 133.2, 130.3, 129.9, 128.8, 126.8, 49.1, 30.0. GC-MS (EI): m/z = 168.6 [M+]. 1-(4-Chlorophenyl)acetone (2i) Yellow oil; yield: 4.20 g (83%). ¹H NMR (600 MHz, DMSO-d ₆): δ = 7.32–7.39 (m, 2 H), 7.14–7.24 (m, 2 H), 3.78 (s, 2 H), 2.13 (s, 3 H). ¹³C NMR (151 MHz, DMSO-d ₆): δ = 205.9, 134.3, 131.9, 131.7, 128.5, 49.0, 29.9. GC-MS (EI): m/z = 168.6 [M⁺].